Dehydroepiandrosterone (DHEA)

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Latest Edit: Iva Lloyd, ND 2021-04-11 (EDT)

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Dehydroepiandrosterone (DHEA) is a steroid sex hormone secreted by the adrenal glands and to a lesser extent, the testes and ovaries. Epidemiological analysis shows that higher DHEA levels are linked to increased life expectancy and well-being. Dehydroepiandrosterone-sulfate (DHEA-S) is the ester form of DHEA. Although DHEA and DHEA-S are the most abundant steroid hormones in the body, their exact function is not completely understood.

DHEA-S levels are not constant throughout the lifespan; levels are high at birth but decline quickly, then increase again at age 8-10 years and peak in the 20s. In the early 30s, levels begin to decline and eventually plateau at age 80 years. DHEA is considered a weak androgen (sex hormone) and its androgenic activity is believed to be related to its conversion to other more potent androgens. All sex hormone production in the body happens through the conversion of DHEA to other estrogen and androgens [1] [2]

Food Sources

  • Animal proteins are the richest dietary source of DHEA.

Uses

The following is a list of the primary uses for DHEA. [1]

  • The cortisol-to-DHEA (cortisol/DHEA) relationship highlights the many facets of stress maladaptation. The cortisol/DHEA ratio helps determine the projected time for recovery, and the substances (hormones, supplements, botanicals) that promote this recovery. The cortisol/DHEA ratio regulates a multitude of functions.
  • Aging: Some studies suggest that DHEA may slow the aging process. Studies have shown that higher levels of DHEA are associated with greater functioning and less dependence in activities of daily living. One study showed that women over the age of 70 who were supplemented with DHEA experienced reduced amounts of bone loss, increased libido, and improvements in skin status.
  • Depression: Low levels of DHEA are found in some individuals with depression. Oral doses of DHEA can improve cognition in middle-aged and elderly individuals with depression. This antidepressant action has been shown in several trials using DHEA. DHEA supplementation appears to be most effective in those who have low levels or a high cortisol:DHEA ratio. DHEA may exert its antidepressant effect by regulating neuronal excitability.
  • Depression associated with Aging: DHEA supplementation can decrease depressive symptomatology in the elderly and increase one's sense of well-being.
  • Hypoadrenalism: It is common for individuals with hypoadrenalism (low adrenal function) to report symptoms of depression and dysthymia. DHEA supplementation can improve mood and sense of well-being in this population.
  • Elevated Cortisol-to-DHEA Ratio: High cortisol levels occur in about 50% of people with depression. This excess in glucocorticoids can lead to decreased learning and memory. DHEA exerts an anti-glucocorticoid action and this may account for its ability to reduce neurocognitive deficits in major depression.
  • Alzheimer's Disease: Although the significance of DHEA in the development of dementia is unclear, a low level of DHEA-S is found in patients with Alzheimer's. Low DHEA-S appears to be a risk factor for the disease. With that said, studies have not shown promising results using DHEA during the treatment of Alzheimer's.
  • Osteoporosis: One study found that women with low DHEA and testosterone due to Addison's Disease had a significantly faster rate of bone loss after menopause compared to healthy postmenopausal women suggesting that these hormones are essential for proper bone mass maintenance. In fact, women with low DHEA-S were 40 times more likely to have osteoporosis than women with normal levels.[1] Supplementation can improve bone turnover and decrease osteoclastic activity.
  • Sexual Function: DHEA supplementation can increase sexual thoughts, interest, and satisfaction in women. Furthermore, erectile dysfunction has been correlated to low DHEA-S levels. Supplementation in this population, especially in those with hypertension and in those individuals where an organic etiology is not suspected, has proven to be effective.
  • Cardiovascular Disease (CVD): DHEA-S levels are found to be significantly lower in men with heart disease than men without; low DHEA-S in men without heart disease at baseline also have an increase risk of developing heart disease. In women, cardiovascular disease risk is highest in women who were in the highest tertile in terms of DHEA-S levels in one study. High DHEA-S is often seen in women with Polycystic Ovarian Syndrome (PCOS) which is also associated with insulin resistance and hypothyroidism, which could explain why high DHEA-S levels are associated with heart disease.
  • Myotonic Dystrophy: Myotonic dystrophy is an inherited disease which affects many systems in the body. It is characterized by muscle weakness and involuntary muscle contraction. It is associated with low DHEA levels. IV administration of DHEA-S has shown improvement in muscle strength and tone, improvement in activities of daily living, and cardiac improvement in patients with this condition.
  • Cancer: Low DHEA levels have also been linked to various types of cancers in women including breast cancer and bladder cancer. This suggests that DHEA may have an anticancer effect and low levels may increase one's risk (except in postmenopausal women). More research is needed to fully delineate the therapeutic use of DHEA in cancer treatment and should be considered with caution in individuals with or at risk of hormone-dependent cancers.
  • Lupus erythematosus (SLE): Supplementation with DHEA has also shown some benefit in individuals with SLE such as decreases in numbers of disease flares and serious SLE-related adverse events. This is like due to DHEA's ability to decrease interleukin-6 (IL-6), a cytokine known as a pathogenic mediator in inflammation and is responsible for stimulating antibody production.
  • Inflammatory Bowel Disease: DHEA-S levels are found to be low in patients with Crohn's Disease and Ulcerative Colitis. Administration of DHEA has shown some improvement in this patient population, allowing some patients to go into remission. This may be a result of DHEA's ability to decrease inflammation.

Prescribing Considerations

The recommended dosages have not yet been established. To determine what your specific requirements are talk to your naturopathic doctor or other trained medical professional.

  • Child and Adolescent: Generally not considered for this population in the absence of such conditions as Addison's disease.
  • Adult: No RDA has been established
  • Supplementation: typical dose is 25-50mg daily (*medical supervision is necessary to monitor for any of the possible adverse effects*) [3]

Note: DHEA is not legally available over-the-counter in certain jurisdictions, including Canada. It can only be acquired through a medical prescription.

Excess Symptoms

  • Excesses in DHEA may lead to masculinization, acne, and hair loss in women or altered secondary sexual characteristics in either gender.

Safety

The safety precautions with DHEA include:

  • Children: DHEA is contraindicated in children and adolescents due to the potential for interference with hormonal regulatory systems and developmental processes.
  • Seniors: DHEA is often prescribed for aging, functional symptoms of aging, and prevention of functional degeneration. Due to the fact that prescription medications also increase with age, the potential for interactions should be considered and special attention to this issue should occur in the elderly population.
  • Pregnancy and Breastfeeding
  • DHEA is contraindicated during this time due to its impact on hormones and potential adverse effects on fetal development.
  • Contraindications
  • DHEA is contraindicated in patients with a personal or family history of prostate cancer, breast cancer, or other hormonally mediated cancer due to its effect on testosterone and estrogen levels. Such a recommendation is based on caution.
  • Drug Interactions:[2]
Supportive or Beneficial:
  • Amlodipine - Drug increases serum DHEA-S and androstenedione levels in some individuals. This action may contribute to beneficial effect on glucose tolerance, insulin sensitivity, and cardiovascular risk.
  • Clonidine and Fluoxetine - DHEA may enhance the activity of these drugs by restoring response of beta-endorphins. Co-administration may be beneficial unless otherwise contraindicated.
  • Corticosteroid, oral - Drug can lower serum levels of DHEA and DHEA-S. DHEA may enhance the activity of prednisolone and counteract some adverse effects associated with long-term steroid therapy.
  • Estrogen/Progestins: Hormone Replacement Therapy and Oral Contraceptives - DHEA and estrogen play mutually supportive roles. Co-administration may be beneficial unless otherwise contraindicated.
  • Methyltestosterone and Related Androgens - Co-administration may enhance therapeutic efforts to increase androgen levels; may be beneficial unless otherwise contraindicated.
  • Zidovudine (AZT) and Related Reverse-Transcriptase Inhibitor (nucleoside) Anti-Retroviral Agents - Co-administration of DHEA to HIV patients with non-major depression on anti-retroviral regimes can significantly improve their psychological state. May be beneficial unless otherwise contraindicated.
Contraindicated:
  • Anticonvulsant Medications, Including Phenobarbital, Phenytoin, and Valproic Acid - Exogenous DHEA may interfere with action of anticonvulsants and could theoretically increase risk of aggressive behaviour by elevating androgen levels. Caution is indicated and concurrent use is contraindicated unless otherwise appropriate.
Other:
  • Alprazolam, Triazolam, and Related Benzodiazepines - Alprazolam has been shown to elevate circulating DHEA. DHEA may reduce hepatic metabolism of these benzodiazepines by inhibiting CYP4A and CYP3A23, potentially raising levels. Clinical significance of this potential interaction is unclear, and supporting evidence is preliminary. Co-administration does not appear to be contraindicated if otherwise appropriate.
  • Anticoagulant Medications - Speculation of potential for increased clotting from DHEA is not substantiated by available evidence. Co-administration does not appear to be contraindicated if otherwise appropriate.

References

  1. 1.0 1.1 1.2 Pizzorno Joseph, Murray Michael (1999) Textbook of Natural Medicine, Elsevier.
  2. 2.0 2.1 Stargrove Mitchell Bebell, Treasure Jonathan, McKee Dwight L (2008) Herb, Nutrient, and Drug Interactions, Clinical Implications and Therapeutic Strategies, Mosby.
  3. Hendler Sheldon S., Rorvik David (Editors) (2001) PDR for Nutritional Supplements, Medical Economics Company Inc.